The localization of signalling molecules to discrete cellular microenvironments via adaptor or scaffolding proteins is emerging as a paradigm to explain the efficiency and specificity of signal transduction cascades. Thus, proteins involved in organizing these """"""""signalsomes"""""""" play a pivotal role in the regulation of intracellular communication. The TRIP6 cDNA encodes a protein with a proline-rich region and three consecutive LIM domains Proline-rich regions have the capacity to interact with Src- homology-3 (SH3) domains and LIM domains also have been characterized as protein/protein interaction motifs. Evidence in Dr. Beckerle's laboratory indicates an association between TRIP6 and another focal adhesion molecule, p130cas. p130cas is a nonenzymatic signalling protein that is tyrosine phosphorylated by Src and focal adhesion kinase in response to integrin- stimulated adhesion and cell migration. Efforts to understand these phenomenon are important because aberrant adhesion and migration can contribute to pathologic physiology such as cancer. In light of these observations, I propose a functional role for TRIP6 as an adaptor protein to coordinate signal transducers involved in integrin-mediated adhesion such as p130cas and other as of yet unidentified proteins. The goal of this proposal plans to determine the relevance of TRIP6 in the regulation of p130cas signalling and cell motility.
The aims of this proposal are to 1) map the-binding domains on TRIP6 and p130cas; 2)assess the effects of disrupting the p130cas/TRIP6 interaction, and 3) identify new TRIP6 binding partners.
